Cystic Fibrosis

June 30, 2014

Vertex Pharmaceuticals issued results of two phase III studies of lumacafto in combination
with ivacaftor in people aged 12 and older with cystic fibrosis (CF) who have two copies (homozygous) of the F508del mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. TRAFFIC and TRANSPORT were two global phase III, randomized, double-blind, placebo-controlled studies, each including two combination treatment groups and one placebo group. The combination
treatment groups evaluated lumacaftor dosed at either 600mg once daily or 400mg every 12 hours (q12h) in combination with ivacaftor dosed at 250mg q12h. 1,108 people enrolled and received at least one dose of study drug in the two studies (549 in TRAFFIC; 559 in TRANSPORT) at approximately 200 sites. Mean absolute improvements in ppFEV of between 2.6 and four percentage points from baseline compared to placebo were observed across the studies (p≤0.0004), with mean relative improvements of 4.3% to 6.7% (p≤0.0007). Vertex plans to submit an NDA in Europe in the fourth quarter of 2014. In the U.S., the combination of lumacaftor and ivacaftor received Breakthrough Therapy Designation in late 2012.

June 16, 2014

Vertex Pharmaceuticals released study
results of ivacaftor for the treatment of
cystic fibrosis (CF) patients who have a
residual function mutation. The first part
of the study included two randomized,
double-blind, placebo-controlled treatment
cycles (part one), and the second part of the
study was an eight-week, open-label period
(part two). The study enrolled 24 people
ages 12 and older with a residual function
mutation. The study met its primary
endpoint as evaluated using a Bayesian
Hierarchical Model (BHM) analysis, which
was supported by analysis using a Mixed
Model for Repeated Measures (MMRM). The
BHM analysis showed a mean absolute improvement
in FEV1 of 2.3 percentage points
compared to placebo, with a 95% credible
interval of 0.38 percentage points to 4.1
percentage points. Results from part one of
the study reflect data from both two-week
treatment cycles for ivacaftor and, separately,
for placebo. The mean baseline lung
function of patients in the study was 67.8%
predicted FEV1, with a range of 37.8% to
108.6% predicted. Ivacaftor was generally
well-tolerated, and the safety and tolerability
results were consistent with those observed
in prior phase III studies of ivacaftor
monotherapy in people with CF who have
the G551D mutation. Vertex plans to initiate
a phase III study of ivacaftor in people
with residual function mutations, pending
discussions with regulatory authorities
regarding the design of the study.

May 26, 2014

PTC Therapeutics released results of a
phase III study of ataluren for treatment of
nonsense mutation cystic fibrosis (nmCF).
The phase III, double-blind, placebo-controlled
study compared ataluren (n=116)
to placebo (n=116) in nmCF patients. The 48-
week trial enrolled 238 patients, ages six and
older, in North America and Europe. Patients
were randomly assigned to one of two
treatment arms: ataluren (10mg/kg morning,
10mg/kg midday, 20mg/kg evening) or
placebo (morning, midday, evening). In
the intent-to-treat population, there was a
3% difference in the relative change from
baseline in %-predicted FEV1 between the
ataluren and placebo groups at week 48
(-2.5% change on ataluren v. -5.5% change
on placebo; p=0.12). An analysis of the
relative change from baseline in %-predicted
FEV1 across all post-baseline study visits
demonstrated an average difference
between ataluren and placebo of 2.5%
(-1.8% average change on ataluren v. -4.3%
average change on placebo; p=0.048). There
were 23% fewer pulmonary exacerbations
in the ataluren group compared to placebo
(p=0.0992). Results of patients not receiving
chronic inhaled tobramycin showed a 5.7%
difference in relative change from baseline
in % predicted FEV1 favoring ataluren, with
a mean change from baseline of -0.7% in the
ataluren arm, and 6.4% in the placebo arm
(nominal p=0.0082). There were 40% fewer
exacerbations in ataluren-treated patients in
this subgroup. Additional studies are in the
planning stages.

April 29, 2013

Vertex Pharmaceuticals released results from a phase II trial of VX-661 and ?ivacaftor for the treatment of cystic fibrosis (CF). This randomized, double-blind, placebo-controlled, dose-escalation study enrolled 128 patients with CF and two copies of the F508del mutation. One group of subjects received VX-661 10mg, 30mg, 100mg or 150mg once daily, or placebo, for 28 days. A second group received a combination of VX-661 10mg, 30mg, 100mg or 150mg once daily and ivacaftor 150mg twice daily, or placebo, for 28 days. Results showed subjects in the VX-661 100mg and 150mg combination dose groups showed statistically significant mean relative improvements in lung function, versus placebo, of 9.0% (p=0.01) and 7.5% (p=0.02), respectively, at Day 28. In contrast, patients who received placebo showed a 0.03% mean relative change in lung function at Day 28 (within-group). VX-661 was well tolerated, both as monotherapy and in combination with ivacaftor. The most frequent adverse events were pulmonary in nature. Based on this data, Vertex plans to conduct additional studies of VX-661 to further evaluate its potential for late-stage development, pending regulatory discussions.

June 18, 2012

PTC Therapeutics issued results from a phase III trial of ataluren for the treatment of nonsense mutation cystic fibrosis. This multinational, double-blind, placebo-controlled study enrolled 238 patients ages six and older. Subjects received ataluren 10mg/kg in the morning, 10mg/kg at midday and 20mg/kg in the evening, or placebo three times daily for 48 weeks. Results showed a 3% difference in the relative change from baseline in percent-predicted FEV1 (forced expiratory volume in one second) between the ataluren and placebo arms at week 48 (-2.5% change on ataluren vs. -5.5% change on placebo; p≡0.124). The drug was well tolerated. The most frequent adverse events occurred in both arms, and included pulmonary exacerbation, cough and upper respiratory tract infection. PTC Therapeutics did not disclose its plans for ataluren.

May 14, 2012

Vertex Pharmaceuticals reported interim results from a phase II study of VX-809 and Kalydeco for the treatment of lung function in adults with cystic fibrosis. This randomized, double-blind, placebo-controlled study enrolled 48 adult patients with cystic fibrosis: 37 who have two copies of the gene F508del and 11 with one or two copies of F508del. Thirty-seven subjects received VX-809 250mg and Kalydeco q12h and 11 subjects received placebo for 56 days. The combination treatment proved statistically significant improvements in lung function relative to baseline compared to placebo (p=0.002). Of subjects who received VX-809 and Kalydeco, approximately 46% (17/37) experienced an absolute improvement from baseline to Day 56 in lung function of 5 percentage points or more, and approximately 30% (11/37) experienced an absolute improvement from baseline to Day 56 of 10 percentage points or more. None of the patients treated with placebo (0/11) achieved a 5-percentage point or more improvement from baseline to Day 56 in lung function. The most adverse events were mild or moderate in severity and comparable between treatment and placebo groups. Vertex Pharmaceuticals plans another combination study of VX-8009 and Kalydeco.

April 4, 2011

Vertex Pharmaceuticals reported results from a phase III trial of VX-770 for the treatment of cystic fibrosis. This two-part, randomized, placebo-controlled, double-blind, parallel-group study, ENVISION, enrolled 52 pediatrics ages 6 to 11, with the G551D mutation in the CFTR gene. VX-770 or placebo was administered as a single 150 mg tablet every 12 hours. The primary endpoint was mean absolute change from baseline in percent predicted FEV1 (forced expiratory volume in one second; lung function) through week 24. Data showed a difference in mean absolute improvement from baseline in lung function of 12.5% and a difference in mean relative improvement from baseline in lung function of 17.4% compared to placebo through week 24 (p<0.0001). Significant improvements in other measures of disease, including weight gain and a reduction in sweat chloride, were also observed through week 24 in the VX-770 treatment arm. The subjects are being followed through 48 weeks.

July 5, 2010

Pharmaxis issued positive results from a phase III trial of Bronchitol for the treatment of cystic fibrosis. This randomized, double blind study (DPM CF302) enrolled 318 subjects across North America, Argentina and Germany. The trial consisted of a 26-week efficacy treatment period followed by a 26-week safety period. The subjects received Bronchitol 400mg twice daily for 52 weeks. The primary endpoint was improvement in lung function, as measured by Forced expiratory volume in one second (FEV1). The primary endpoint showed improvement over placebo at 26 weeks but did not reach statistical significance (p≡0.059). Subjects treated with Bronchitol had an 8.2 % improvement in FEV1 compared to baseline over the 26 weeks of the study which was highly significant (p<0.001). These improvements from baseline were seen at six, 14 and 26 weeks of treatment (p≤0.001). Secondary endpoints targeting other measures of lung function also showed significant improvement in patients on Bronchitol compared with control, including forced vital capacity (FVC) (p≡0.022), and FEV1 % predicted (p≡0.024).

February 8, 2010

Vertex issued positive results from a phase IIa trial of VX-809 for the treatment of cystic fibrosis (CF). This randomized, double-blind study enrolled 89 adult subjects homozygous for the F508del mutation. The subjects received once daily doses of VX-809 (25 mg, 50 mg, 100 mg or 200 mg) or placebo, in addition to standard therapies, for 28 days. At both the 100 mg and 200 mg dose levels, a statistically significant decline in sweat chloride, a diagnostic hallmark that occurs in all CF patients, was observed compared to placebo (-6.13 mmol/L and -8.21 mmol/L , respectively). A dose response for change in sweat chloride was observed across all four dose groups. VX-809 was well-tolerated across all treatment arms.

May 11, 2009

Pharmaxis issued positive results from a phase III trial of Bronchitol for the treatment of cystic fibrosis. This randomized, double blind, placebo controlled study enrolled 324 subjects in the United Kingdom, Ireland, Australia and New Zealand. The subjects received Bronchitol 400 mg twice per day for six months. The primary endpoint assessed whether Bronchitol improved lung function as measured by a change in Forced Expiratory Volume in 1 second (FEV1), over the six month period. This endpoint was reached; Bronchitol led to a statistically significant improvement in lung function from baseline of 6.6% (p≡0.001 versus placebo). Lung function improved at week six and was sustained through to week 26. The key secondary endpoint was to assess whether Bronchitol further improved lung function in subjects already being treated with dornase alfa (Pulmozyme), the current standard of care. This endpoint was also successfully achieved; FEV1 improved after six months by 5.2% from baseline (p≡0.002 versus placebo). Over the six month treatment period, there was significant lung function improvement for both those subjects being treated with Bronchitol and dornase alfa (p≡0.008 versus placebo) and those being treated with Bronchitol alone (p≡0.015 versus placebo).

August 18, 2008

Altus released positive results from a phase III trial of Trizytek for the improvement of fat absorption in subjects with cystic fibrosis and pancreatic insufficiency. This multi-center, randomized, double-blind, placebo-controlled international study enrolled 163 subjects over the age of seven with cystic fibrosis and exocrine pancreatic insufficiency. The subjects received one Trizytek capsule per meal. The primary endpoint was the efficacy of Trizytek in the improvement of fat malabsorption through the measurement of coefficient of fat absorption (CFA). In the overall Trizytek treatment group there was an improvement in the mean CFA of 11.3 (36% change from baseline) while subjects on placebo remained relatively unchanged, with a mean CFA of 0.2 (4% change from baseline). The mean difference between groups for the change in CFA was 10.6 (p=<0.001). In a sub-group of subjects with severe malabsorption (baseline CFA below 40), Trizytek led to an improvement in the mean CFA of 20.2 (80% change from baseline), while in the placebo group there was an increase in mean CFA of 5.1 (24% change from baseline). The mean difference between groups for the change in CFA was 15.1 (p=<0.001). Main secondary endpoints were also reached. The subjects treated with Trizytek had a statistically significant improvement in coefficient of nitrogen absorption compared to placebo (p =<0.001) and there was a significant decrease in stool weight in the Trizytek treated group compared to placebo (p=0.001). However, overall top-line results were affected by a marked difference between subjects within the U.S. and outside of the U.S. Three out of six non-U.S. countries did not show a difference between Trizytek and placebo groups. Altus planned to investigate the possible factors for these differences. Trizytek was determined to be safe and well tolerated. Two long-term safety trials are currently underway.

Pharmaxis issued positive results from a phase II trial of Bronchitol for the treatment of cystic fibrosis. This open-label, randomized study enrolled 48 subjects with cystic fibrosis in Canada and Argentina. The subjects received 400mg, 240 mg, 120 mg and 40 mg of Bronchitol inhaled twice a day for 14 days in a crossover design. The primary endpoint was a dose dependent improvement in lung function as measured by FVC (forced vital capacity) and FEV1 (Forced expiratory volume in one second). At the end of the two-week treatment periods, changes in lung function were as follows: in the 400 mg treatment group FEV1 increased by 8.6% (139 mls, p=0.0006 versus 40 mg), in the 240 mg treatment group FEV1 increased by 4.6% (87 mls), in the 120 mg treatment group FEV1 increased by 3.7% (42 mls) and in the 40 mg treatment group FEV1 decreased by -1.6% (-33 mls). FVC changed by +7.9% on 400 mg (p=0.0004 versus 40 mg), +3.9% on 240 mg, +1.5% on 120 mg and -0.6% on 40 mg. Secondary endpoints included maximum mid expiratory flow (MMEF) and quality of life measures. These measures also showed a positive effect for 400 mg Bronchitol on MMEF and the respiratory domain of the cystic fibrosis quality of life questionnaire (CFQR). Bronchitol was well tolerated. Based on the results the 400 mg Bronchitol dose will be used in upcoming phase III studies.

July 28, 2008

Aradigm released positive results from a phase II trial of inhaled liposomal ciprofloxacin for the treatment of Pseudomonas Aeruginosa infections in patients with cystic fibrosis. This open-label study enrolled 22 subjects with cystic fibrosis in Australia and New Zealand. Following an antibiotic washout period, subjects received inhaled liposomal ciprofloxacin once daily for 14 consecutive days. Data are from 21 subjects who completed the study. The primary endpoint was the change from baseline in the sputum Pseudomonas Aeruginosa colony forming units (CFU), Pseudomonas CFU decreased by a mean 1.43 log over the 14-day treatment period (p less than 0.0001) . One week after treatment ended, Pseudomonas bacterial density in the lung was still reduced by 1.02 log CFU from the baseline without additional antibiotic use. Pulmonary function testing, as measured by the forced expiratory volume in one second (FEV1), showed a significant mean increase of 6.86 % from baseline after 14 days of treatment (p=0.04). The study drug was well tolerated, with no serious adverse events reported. Based on the results, Aradigm plans to advance the development of liposomal ciprofloxacin for cystic fibrosis into the United States.

June 16, 2008

Inspire issued positive results from a phase III trial of denufosol tetrasodium for the treatment of cystic fibrosis. This randomized, double-blind trial, dubbed TIGER-1 (Transport of Ions to Generate Epithelial Rehydration), enrolled 352 subjects, aged 5 years and above, in the U.S. The subjects received 60 mg of denufosol or placebo by inhalation three times daily for a 24-week placebo-controlled efficacy treatment period. This was followed by a 24-week open-label safety extension period. The primary endpoint was change from baseline in Forced Expiratory Volume in one second (FEV1), in liters, at the 24-week time point. This endpoint was reached with statistical significance in the denufosol arm compared to placebo (45 milliliter treatment group difference, p = 0.047). The treatment effect of denufosol increased over the 24-week placebo-controlled period and during the extension period from weeks 24 to 48. A key secondary endpoint was also evaluated in the trial. There was a trend in differences in Forced Expiratory Flow 25%-75% (FEF 25%-75%) favoring denufosol over placebo (p = 0.072). Treatment was well tolerated, with adverse event profile similar to placebo. The open label portion of the study is currently underway and results are expected in Q1 of 2009.

March 31, 2008

Vertex issued positive interim results from a phase IIa trial of VX-770 for the treatment of cystic fibrosis. Results are from twenty subjects with the G551D mutation in Cystic Fibrosis Transmembrane Conductance Regulator (CFTR). The subjects received either VX-770 or placebo in addition to standard therapies for fourteen days as part of the trial's blinded, randomized, crossover design. Four subjects received placebo during both fourteen-day dosing periods; eight subjects received 25 mg of VX-770 twice-daily during one period and 75 mg in the other; and eight subjects received 75 mg of VX-770 twice-daily during one period and 150 mg during the other dosing period. There was a one to four week wash-out between each dosing period. The primary endpoints, lung function, sweat chloride and Nasal Potential Difference, were all reached. Lung function was assessed with a standard test, FEV1 (Forced expiratory volume in one second). Over the fourteen-day dosing period subjects receiving the highest dose of VX-770 (150mg twice daily) showed a mean increase from baseline in FEV(1) of 10.1%, or 0.22L (p less than0.008). In contrast, subjects receiving placebo showed a slight decrease in FEV(1) (less than 1%; 0.03L). In addition, in the VX-770 (150mg twice daily) group, sweat chloride levels decreased from a mean 95.5 mmol/L at baseline to 53.2 mmol/L at day fourteen (p less than0.0001). Six of eight subjects in the 150 mg dose group achieved a decrease in sweat chloride to below 60 mmol/L. There was no notable change in sweat chloride in subjects receiving placebo. Nasal Potential Difference (NPD), which measures chloride ion secretion, was also improved after day fourteen in the VX-770 (150 mg twice daily) dose group. This arm showed a significant mean change from baseline in chloride ion secretion in NPD of -5.4 mV (p=.01). In contrast, in those treated with placebo, a mean change of -1.74 mV was observed. Treatment was determined to be well tolerated. Based on the results, Vertex plans to move into the second part of this trial which will assess dosing of VX-770 or placebo for twenty-eight days.

June 4, 2007

Gilead issued positive results from a phase III trial of aztreonam lysine for the treatment of cystic fibrosis and concurrent pulmonary Pseudomonas aeruginosa infection. This double-blinded randomized trial, dubbed AIRCF-1 enrolled 164 subjects who received aztreonam lysine (75 mg) or placebo three times daily for 28 days. The primary endpoint was change from baseline in respiratory symptoms, as assessed by the Cystic Fibrosis Questionnaire-Revised (CFQ-R). Results revealed a significant improvement in the CFQ-R, with a mean change from baseline of 9.7 points compared to placebo (p less than 0.001). Respiratory function, as measured by improvement of forced expiratory volume in one second (FEV1) was also improved. At day 28 subjects in the aztreonam lysine group with a mean change from baseline of 10.3% versus placebo (p less than 0.001). Based on positive phase III results, Gilead plans to submit a NDA to the FDA in the second half of 2007.

Pipex released positive results from a phase I/II trial of Coprexa for the treatment of refractory Idiopathic Pulmonary Fibrosis (IPF). This open-label trial enrolled 20 subjects with IPF and evidence of disease progression despite treatment with prednisone +/- cytotoxic therapy. Subjects received Coprexa (20mg) orally twice a day with meals plus 20-40mg orally at bedtime, for one year. Through-out the treatment duration subjects were monitored for adverse events, change in pulmonary function as measured by percent predicted forced vital capacity (FVC), diffusing capacity of the lung for carbon monoxide (DLco) and walk distance (six minute walk test). Treatment was generally well tolerated. FVC was stable in 60% of subjects, improved in 10% of subjects and worsened in 30% of subjects. DLco remained stable in 75% of the subjects and improved in 5%. DLco fell in 20% of subjects. At 1 year, the 6 minute walk test improved from 611 feet to 735 feet. Based on the results, Pipex plans to initiate an additional twelve month, multi-center, randomized, double-blind, placebo-controlled trial of Coprexa later in 2007.

March 12, 2007

AOP Orphan Medical and Lantibio reported positive results from a phase II trial of Moli1901, an aerosolized therapy for the treatment of cystic fibrosis. This double-blind, placebo controlled trial enrolled adolescents aged 12 and older and adults, who received daily administration of Moli1901 or placebo for 28 days. Moli1901 was found to be well tolerated. The pharmacokinetic profile revealed limited to no systemic absorption of Molo1901 as no traces of the drug were detected in the plasma of subjects. The median forced expiratory volume in one second (FEV1) change from day 1 to the final evaluation on day 56 amounted to -3% in the placebo group and 2% in the Moli1901 group (p=0.0217). Based on the results, AOP Orphan and Lantibio plan to move forward with larger phase II efficacy trials.

November 13, 2006

Inspire reported positive results from a phase II trial of denufosol tetrasodium inhalation solution for the treatment of cystic fibrosis in pediatrics. This double-blind, randomized, placebo-controlled, parallel group trial enrolled 13 subjects, aged five to seven years. Subjects were administered 20 mg or 60 mg of denufosol tetrasodium or placebo, three times a day for 28 days. Treatment was well tolerated at both dose levels with a safety profile similar to placebo. The most commonly reported adverse event was cough. In addition, the subjects were able to reliably perform the lung function tests to measure FEV1 (Forced Expiratory Volume in one second). Based on the data, Inspire plans to include this pediatric age group in future phase III trials of denufosol tetrasodium.

October 31, 2005

Altus Pharmaceuticals reported positive results of a phase II trial of TheraCLEC (ALTU-135), for the treatment of cystic fibrosis patients with malabsorption due to pancreatic insufficiency, at the North American Cystic Fibrosis Conference in Baltimore. Trial data yielded statistically significant improvements in absorption of both dietary fat and protein (p<0.001), and additional improvements in carbohydrate absorption. The subset of patients with the lowest baseline absorption rates showed the greatest improvements. This dose-ranging, randomized, double-blind study enrolled 125 subjects across 26 sites in the US. The company announced that, based on these results, they had begun meetings with the FDA regarding the design of phase III trials of the drug.

September 5, 2005

Pharmaxis has announced positive results of a phase II trial, dubbed DPM-CF-201, of Brohchitol, for the treatment of cystic fibrosis. Trial data met their primary efficacy endpoint, significantly improving forced lung ejection volume in 1 second (FEV1) by 7% after 2 weeks, compared to no improvement for placebo (p=0.008). Secondary efficacy was also noted in reducing the severity of respiratory symptoms (p<0.02). No serious adverse events were reported. This randomized, double-blind, placebo-controlled crossover study enrolled 49 cystic fibrosis patients across 8 sites in Australia and New Zealand, who received Bronchitol or placebo twice daily for 14 days.

July 4, 2005

PTC Therapeutics announced positive results of a pair of phase I studies of PTC124, their investigational drug targeting nonsense mutations in cystic fibrosis (CF) and Duchenne muscular dystrophy (DMD), at the 28th Annual European Cystic Fibrosis Conference. Trial data met primary safety and pharmacokinetic endpoints: no serious adverse events were reported, overall tolerability was positive, target plasma concentrations were achieved, and an optimal dosing regimen for future trials has been established. Pharmacogenetic analysis indicated that the drug did not induce unintended read-through of normal, healthy stop codons. These single- and multiple-dose studies enrolled healthy volunteers. The company announced plans to initiate phase II studies of the drug for the treatment of CF, based on these results.

April 18, 2005

Neuro3d has announced positive results of a pair of phase II trial of their investigational antipsychotic ocaperidone, for the treatment of schizophrenia. Data from both studies yielded strong evidence of efficacy, with significant improvement in all primary efficacy measures, including both positive (e.g. hallucinations) and negative (e.g. social withdrawal, emotional flatness) symptom severity scores on the PANSS, BPRS and CGI diagnostic scales, vs. placebo. The drug also demonstrated non-inferiority of efficacy vs. an approved antipsychotic, and significant relative superiority in reducing drug-induced weight gain. The first trial, a double-blind, placebo-controlled safety and efficacy study, randomized 127 patients to receive dose ranging regimens of ocaperidone (0.1 mg-0.6 mg) or placebo daily for 8 weeks. The second was an active-controlled approved-therapy comparison study which enrolled 105 subjects, who received ocaperidone or an approved atypical antipsychotic for the treatment daily for 12 weeks. The company announced that these data would form the basis of phase III trials in the near future.

PTC Therapeutics announced results of a phase I study of PTC124, for the treatment of Duchenne muscular dystrophy (DMD) and cystic fibrosis (CF). Results from the study yielded a positive safety profile, with no symptomatic drug-related adverse events at any dose level and minor, reversible laboratory changes noted in some subjects. Preliminary pharmacokinetic data indicated that administration at safe dosing levels was able to produce drug plasma concentrations associated in preclinical studies with activity against the conditions. This open-label study treated healthy volunteers with twice daily PTC124 at multiple dosing levels (up to 50 mg) for 14 days. Based on these results, the company announced that they were working with FDA regulators to finalize the design of upcoming phase II trials.

March 21, 2005

NicOX announced positive results of a phase IIa trial of NCX 1020, a nitric oxide donating derivative of the approved inhaled corticosteroid budesonide, for the treatment of asthma. Data yielded a trend towards efficacy in the primary endpoint, with a reduced incidence of bronchoconstriction at 4 hours following methacholine challenge (an effect not observed with the approved drug). Pharmacokinetic data demonstrated reduced peak plasma concentrations and delayed peak systemic absorption rates of budesonide versus an approved budesonide formulation, which the company hopes will lead to fewer systemic side effects. This double blind, 3-way cross over trial enrolled 12 asthmatic patients at the Department of Asthma, Allergy and Respiratory Science of King's College London, who were randomized in days 1, 4, and 7 to receive a single-dose of either NCX 1020 (600 mcg), budesonide (400 mcg) and placebo.

Targeted Genetics has issued the results of a phase II study of tgAAVCF, for the treatment of cystic fibrosis. Results from the study indicated that the drug failed to meet its primary endpoint, with no significant improvement in forced expiratory volume in 1 second (FEV1), a measure of lung function, following 30 days of treatment, vs. placebo. This double-blind, randomized, placebo-controlled study enrolled a total of 102 patients, who were randomized to receive two doses of either 1x1013 DNAse resistant particles of tgAAVCF (n=51) or placebo (n=51) via nebulizer at day 0 and day 30, and were evaluated for FEV1 every 2 weeks for 90 days. Analysis of data regarding secondary safety and efficacy endpoints, including FEV1 at 60 and 90 days, are ongoing, and the company hopes to announce complete safety and efficacy results for this trial later this year.

October 25, 2004

Corus Pharma announced positive results of a phase II trial of Corus 1020 (aztreonam lysinate), for the treatment of cystic fibrosis (CF)-related respiratory infections, at the 18th Annual North American Cystic Fibrosis Foundation conference. Trial data indicated that the drug was efficacious in alleviating Pseudomonas aeruginosa infections in patients with CF, with subjects in both dosing groups achieving a 97% or greater reduction in sputum bacterial density, compared with baseline. Significant secondary improvement was seen in respiratory function, with the lower dose producing a more consistent response. Both regimens were safe and generally well tolerated, though the high-dose regimen did show a trend towards increased respiratory symptoms including cough. This double-blind, placebo-controlled study randomized 105 CF patients with Pseudomonas aeruginosa infections to receive one of two twice-daily regimens of the drug (75 mg or 225 mg) or placebo for two weeks. Based on these results, Corus announced plans to initiate phase III studies with the 75 mg. regimen in the near future.

October 18, 2004

Chiron Corporation and Nektar Therapeutics reported the results of a phase I safety, pharmacokinetic and delivery-time trial of their inhalable powder formulation of tobramycin (TPI), for the treatment of Pseudomonas aeruginosa (Pa) respiratory infections in patients with cystic fibrosis, at the 18th Annual North American Cystic Fibrosis Foundation in St. Louis, Missouri. The trial data found that TPI offered preliminary evidence of non-inferior efficacy, compared to other approved formulations of tobramycin, and offered a drastically reduced treatment burden over these current therapies. The drug was also shown to be well tolerated in this formulation. The trial enrolled 90 cystic fibrosis subjects suffering from Pa respiratory infections, who were randomized to receive either TPI via portable hand-held inhaler or therapy with TOBI, Chiron’s approved tobramycin formulation delivered via nebulizer. Chiron announced plans to initiate two phase III trials of TPI, based on these data.

May 3, 2004

Inspire Pharmaceuticals reported positive results from a phase II trial investigating INS37217 Respiratory, a P2Y2 agonist for the treatment of cystic fibrosis (CF). Results showed that subjects receiving INS37217 had significantly better lung function compared with placebo. All three doses of INS37217 were well tolerated with the most common adverse event being cough. The double-blind, placebo-controlled, randomized study enrolled 90 subjects with CF at 14 sites in the U.S. Subjects received INS37217 or placebo three times daily for 28 days by standard jet nebulizer. It was designed to determine the tolerability of INS37217 in doses up to 60mg. Additional data will be reported at the 18th Annual North American Cystic Fibrosis Conference in St. Louis.

March 1, 2004

Debiopharm and Dyax reported positive results from a phase IIa trial investigating DX-890, an inhibitor of human neutrophil elastase for the treatment of cystic fibrosis. Preliminary results demonstrated the drug produced good tolerability and the expected pharmacological effects. Data showed that 20 subjects responded to treatment as demonstrated by decreases in hNE activity in sputum. DX-890 was well tolerated, with only minor treatment related side effects. The open label study enrolled 34 pediatric subjects with cystic fibrosis in Europe. The trial used four dosages of a nebulized formulation of DX-890 (1 mg/ml in week 1, 2.5 mg/ml in week 2, 5 mg/ml in week 3, and 10 mg/ml in week 4). The companies plan to conduct a larger multicenter phase IIb study later this year.

October 20, 2003

Genaera and Cystic Fibrosis Foundation Therapeutics reported negative results from a phase II trial investigating Lomucin (talniflumate), a mucoregulator for the treatment of cystic fibrosis. Results showed the drug failed to improve pulmonary function. Data also demonstrated no improvement in residual volume measures of neither pulmonary function nor improvement in pulmonary symptoms as measured by the Acute Respiratory Illness Checklist. The randomized, double-blind study enrolled 55 subjects and was conducted in Ireland. Subjects were treated with, 740 mg of Lomucin three times daily for four weeks, or placebo. Results were reported in October 2003, at the North American Cystic Fibrosis Conference in Anaheim, Calif.

July 22, 2002

Millennium Pharmaceuticals and Taisho Pharmaceutical have discontinued the development of oral MLN977 for chronic asthma based on phase II trial results. The four-week, double-blind, dose-finding trial was conducted at 35 sites and included 193 subjects. Subjects were randomized to receive placebo or 200 mg, 400 mg or 600 mg of MLN977 and dosed once daily. After 14 to 28 days of dosing, MLN977-treated subjects experienced statistically significant improvements in FEV1. However, three subjects experienced elevations in liver enzymes that were most likely drug-related. The effects on liver function were similar to those reported with previously developed 5-lipoxygenase (5-LO) inhibitors; MLN977 is a second generation compound in this class of therapies.

Positive results were reported from a phase IIa trial of Dyax and Debiopharm S.A.'s DX-890 in adult subjects with cystic fibrosis (CF). The trial was implemented in two stages with DX-890 doses given by daily inhalation for 14 days. In the first study segment, seven CF subjects received 7.5 mg of DX-890 per treatment. DX-890 was well tolerated; six subjects completed therapy with no change in pulmonary function tests. Inhibition of elastase in sputum was also observed. In the second study segment, 19 CF subjects received 30 mg of DX-890 per treatment. The drug was once again well tolerated - 11 subjects received a full course of treatment, and for these subjects, pulmonary function tests did not show any adverse changes compared to baseline. These subjects also experienced inhibition of sputum neutrophil elastase following treatment, with seven of the 11 experiencing complete inhibition.